Koldamova Radosveta, Lefterov Iliya
Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15219, USA.
Curr Alzheimer Res. 2007 Apr;4(2):171-8. doi: 10.2174/156720507780362227.
Studies, ranging from epidemiological to in vitro and in vivo experimental settings have provided convincing evidence that different aspects of brain lipid metabolism may influence Alzheimer disease pathogenesis through effects on beta-amyloid deposition and clearance. It has been demonstrated that transcription factors called nuclear liver X receptors (LXR) and their responsive genes provide natural regulatory mechanisms and influence AD pathogenesis through their modulatory effects on intracellular cholesterol content, cholesterol efflux and possibly via anti-inflammatory mechanisms. Here, we provide a brief summary of the approaches undertaken by different groups that lead to the nowadays working model of LXR and ABCA1 regulatory role in brain amyloidogenesis and amyloid clearance and we highlight the therapeutic potential of LXR agonists.
从流行病学研究到体外和体内实验研究,均提供了令人信服的证据,表明脑脂质代谢的不同方面可能通过对β-淀粉样蛋白沉积和清除的影响来影响阿尔茨海默病的发病机制。已经证明,称为核肝X受体(LXR)的转录因子及其反应性基因提供了天然调节机制,并通过其对细胞内胆固醇含量、胆固醇外流的调节作用以及可能通过抗炎机制影响阿尔茨海默病的发病机制。在此,我们简要总结了不同研究团队所采用的方法,这些方法形成了目前关于LXR和ABCA1在脑淀粉样蛋白生成和淀粉样蛋白清除中的调节作用的工作模型,并且我们强调了LXR激动剂的治疗潜力。